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The study of tactile illusions like visual illusions can reveal the brain's processing strategies. A famous tactile illusion is the cutaneous rabbit illusion. Fundamental to this illusion is the perceptual length contraction phenomenon: two taps that occur in rapid succession on the forearm are perceived as occurring closer together than they were physically placed. Our lab previously proposed a Bayesian probabilistic model that views perception as a compromise between expectation (prior experience) and sensation (likelihood of sensorineural data given hypothesized tap locations). The model proposes a low-speed prior, an expectation based on experience that objects tend to be stationary or to move slowly on the skin. When the sensation of space is unclear (e.g., taps are weak), the model predicts that expectation will strongly influence perception. Consistent with this prediction, our lab previously showed that the use of weaker taps causes more pronounced perceptual length contraction. Here we report psychophysical tests on 64 participants, which confirmed this finding. Our study also used stimulus sequences consisting of a weak and a strong tap, for which the Bayesian model predicts an asymmetric perceptual length contraction, such that the weaker tap location will be perceived to shift more than the stronger tap. The experimental results confirmed this prediction, providing further support for our Bayesian probabilistic model as an explanation for perceptual length contraction. However, our results revealed a discrepancy in the data at the smaller SOAs, which showed less length contraction than predicted. We hypothesized that participants might overestimate the smaller SOAs, an effect our lab defines as time dilation. Accordingly, in a second study we investigated the effects of varying SOA and lengths on perceived SOA. The model predicts more pronounced time dilation at smaller SOAs and larger lengths. The psychophysical data from 37 participants confirmed the trends predicted by the model. / Thesis / Master of Science (MSc)

In der vorliegenden Arbeit werden die Ergebnisse von Stent Implantationen bei Kindern mit angeborenen Herzfehlern an der Humboldt Universität zu Berlin, Charité vorgestellt. Zwischen 1994 und 2001 wurden bei 103 Patienten 146/149 Stents erfolgreich in 115 Gefäßstenosen oder Ductus arteriosus implantiert. Das Alter der Patienten bei der Implantation lag zwischen einem Tag und 34 Jahren (ein erwachsener Patient), im Mittel 4 Jahre, Median 1,1 Jahre; das Körpergewicht lag zwischen 1,75 kg und 75 kg, im Mittel 14,4 kg bei einem Median von 7,5 kg. Von den 149 Stents wurden 39,5% in periphere Pulmonalarterienstenosen, 17,5% in Aortenisthmusstenosen, 28,5% in den Ductus arteriosus, 8,5% in Systemvenenstenosen und 6% in Pulmonalvenenstenosen. 40% der 146 erfolgreich implantierten Stents wurden palliativ, 60% kurativ implantiert. Während eines Nachbeobachtungszeitraumes von einem Monat bis 7,5 Jahren, im Mittel 2,14 Jahren, wurden 60 der implantierten Stents insgesamt 79 mal redilatiert. 15 dieser Stents zweimal und 4 dreimal. Der häufigste Grund für eine Redilatation war das Körperwachstum der Patienten (58%). In-Stent Restenosen aufgrund von Intima-Proliferation führten in 25,5% zu einer Redilatation, die übrigen 16,5% Restenosen wurden durch Kompression von außen verursacht. Bei der vorliegenden Studie zeigte sich, dass die Stent-Implantation nicht nur eine effektive Methode zur Behandlung von Gefäßstenosen bei Patienten mit angeborenen Herzfehlern ist. Vielmehr gilt sie bei dem vorgestellten Patientengut als: 1. Vorbereitung, Erleichterung oder Ermöglichung von korrigierenden Operationen bei Neugeborenen durch palliativen Stent Einsatz in den Ductus arteriosus, Aortenisthmusstenosen oder in interventionell eröffnete rechtsventrikuläre Ausflußtrakte; 2. Vermeidung komplexer chirurgischer Eingriffe durch Stent Implantationen in native Aortenisthmusstenosen oder in den Ductus arteriosus bei Patienten mit kritischer Pulmonalstenose oder- atresie mit intaktem Ventrikelseptum; 3. Verbesserung post-operativer Ergebnisse und damit Verbesserung der langfristigen Prognose durch Beseitigung post-operativer Restenosen, zum Beispiel peripherer Pulmonalstenosen nach operativer Korrektur einer Fallotschen Tetralogie. Darüber hinaus lassen sich mit Hilfe von Stents komplexe chirurgisch/interventionelle Therapiestrategien, zum Beispiel dem Etablieren einer Fontanzirkulation, verwirklichen. Da in den meisten Fällen ein lebenslanger Verbleib der Stents geplant war wurden ausschließlich ballonexpandierbare Stents implantiert. Diese können, dem Alter und dem Körperwachstum der Patienten entsprechend durch Redilatation angepaßt werden. Diese limitierten Langzeit-Ergebnisse erscheinen diesbezüglich vielversprechend. Dagegen sind die Ursachen der In-Stent Restenosen aufgrund von Intima-Proliferation, die bei einigen Kindern gefunden wurden, noch nicht verstanden und bedürfen weiterer Untersuchungen. Eine Limitation der vorgestellten Methode besteht in der Stent-Technologie. Derzeit stehen keine Stents zur Verfügung, die im Neugeborenenalter implantiert werden können und bis zum Abschluß des Größenwachstums der Patienten eine gefäßstützende Funktion gewährleisten. Neue Stent-Technologien sind daher für den kurativen Einsatz bei Neugeborenen und kleinen Säuglingen erforderlich und werden in dieser Arbeit im Tiermodel vorgestellt. Zwei unterschiedliche neu Stents, die von zwei unabhängigen Herstellern entwickelt wurden, können durch eine Miniaturisierung der Einführungssysteme im Neugeborenenalter eingesetzt werden und ermöglichen eine Erweiterung der gestenteten Gefäßdurchmesser von minimal 4 Millimeter auf über 20 Millimeter. Weitere chronische Untersuchungen im Tiermodel sind notwendig bevor diese neuen Stent-Technologien in die klinische Erprobung bei Neugeborenen mit angeborenen Herzfehlern eingeführt werden können. / This study reports on stent implantation in paediatric patients with congenital heart disease at the department of paediatric cardiology, Humboldt university of Berlin, Charité. Between 1994 and 2001 146/149 stents were successfully implanted in 115 lesions or arterial ducts of 103 patients. The age of the patients ranged between 1 day and 34 years (one adult patient), mean 4 years, median 1.1 years; the bodyweight was measured between 1.75 kg and 75 kg, mean 14.4 kg, median 7.5 kg. The stent were implanted into different lesions: 39.5% in peripheral pulmonary artery stenoses, 17.5% in coarctation, 28.5% in the arterial duct, 8.5% in systemic vein stenoses and 6% in pulmonary vein stenoses. The implantations were performed for palliativ reasons in 40% or as a definite treatment in 60%. During a follow up period between 1 months and 7.5 years, mean 2.14 years 79 repeat dilations were performed on 60 stents, 15 stents twice and 4 stents three times. The most common reason for repeat intervention were dilation according to patients growth (58%). In-stent restenoses due to intimal hyperplasia were noted in 25.5% and 16.5% restenoses occurred due to compression from surrounding structures. The results of this study demonstrated stent-implantation not only as an effective method for treatment of vessel stenosis in young patients with congenital heart diseases. In addition 1. palliative stenting of the arterial duct, critical coarctation or right ventricular outflow tract obstruction in neonates improves surgical outcome or increases operability. 2. stent implantation can be an attractive alternative to complex surgery i.e. the establishment of Fontan circulation as part of a combined surgical/interventional concept 3. postoperative stenting of restenosis improves surgical results and reduces mortality and morbidity by reduction of the individual number of surgical procedures. Balloon expandable stents were used exclusively as the vast majority were considered to treat vessel stenosis for a lifelong period. The limited experiences on long-term follow-up are encouraging concerning the possibility of repeat dilation according to patients growth. However, the mechanisms of in-stent restenosis are not fully understand. For long-term treatment of vessel stenosis in neonates and small infants the conventional stent technology was found as a major limitation. New stent-designs are necessary. The report encloses two different new stent-technologies in animal studies. Miniaturised stents and delivery systems developed by two different companies are demonstrated. An additional advantage of the new stent designs is the broad variability of the stent diameters. After the initial implantation with a minimum diameter of 4 millimetres those stents can be dilated to a maximum diameter of more than 20 millimetres. Further investigations are necessary to demonstrate the efficacy of the new stent designs in different lesions of human neonates.

As hard rock mining progresses into higher stress mining conditions through either late stage extraction or mining at depth, the rock mass is driven not just to the peak strength, but often well into the post-peak until complete ‘failure’ occurs and easier mining conditions become evident. Limited research has been accomplished in identifying the transition of the rock mass and its behaviour into the post-peak and this research investigates this behaviour in detail. As the rock mass progressively fails, fractures are initiated through intact rock and extension and shear failure of these and pre-existing features occurs. Associated with this failure are microseismic events, which can be used to give an indication of the strength state of the rock mass. Based on an analogy to laboratory testing of intact rock and measurement of acoustic emissions, the microseismicity can be used to identify, fracture initiation, coalescence of fractures (yield), localization (peak-strength), accumulation of damage (post-peak) and ultimate failure (residual strength) leading to aseismic behaviour. The case studies presented in this thesis provide an opportunity to examine and analyse rock mass failure into the post-peak, through the regional and confined failures at the Williams and the Golden Giant mines, both in the Hemlo camp in Northern Ontario, Canada. At the Williams mine, the progressive failure of a sill pillar region into the post-peak was analysed; relating the seismic event density, combined with numerical modelling and a spatial and temporal examination of the principal components analysis (PCA), to characterize the extent, trend and state of the yielding zone, which formed a macrofracture shear structure. Observations of conventional displacement instrumentation, indicates regional dilation or shear of the rock mass occurs at or prior to the point of ‘disassociation’ (breakdown of stable PCA trends) when approaching the residual strength. At the Golden Giant mine, the complete process from initiation to aseismic behaviour is monitored in a highly stressed and confined pendent pillar. The PCA technique, numerical modelling and focal mechanism studies are used to define significant stages of the failure process, in which a similar macrofracture structure was formed. Temporal observations of key source parameters show significant changes prior to and at the point of coalescence and localization.

In vivo, la pression artérielle au niveau des artères cérébrales est pulsée, alors que ex vivo, l’étude de la fonction cérébrovasculaire est majoritairement mesurée en pression statique. L’impact de la pression pulsée sur la régulation du tonus myogénique et sur la fonction endothéliale cérébrale est inconnu. Nous avons posé l’hypothèse selon laquelle en présence d'une pression pulsée physiologique, la dilatation dépendante de l’endothélium induite par le flux et le tonus myogénique seraient optimisés. L’objectif de notre étude est d’étudier ex vivo l’impact de la pression pulsée sur le tonus myogénique et la dilatation induite par le flux dans les artères cérébrales de souris. Nous avons utilisé un artériographe pressurisé couplé à un système générant une onde pulsée de fréquence et d’amplitude réglables. Les artères cérébrales moyennes (≈160 μm de diamètre) ont été isolées de souris C57BL6 âgées de 3 mois et pressurisées à 60 mm Hg, en pression statique ou en pression pulsée. En pression statique, le tonus myogénique est faible mais est potentialisé par le L-NNA (un inhibiteur de la eNOS) et la PEG-catalase (qui dégrade le H2O2), suggérant une influence des produits dilatateurs dérivés de la eNOS sur le tonus myogénique. En présence de pression pulsée (pulse de 30 mm Hg, pression moyenne de 60 mm Hg, 550 bpm), le tonus myogénique est significativement augmenté, indépendamment du L-NNA et de la PEG-catalase, suggérant que la pression pulsée lève l’impact de la eNOS. En pression statique ou pulsée, les artères pré-contractées se dilatent de façon similaire jusqu’à une force de cisaillement de 15 dyn/cm2. Cette dilatation, dépendante de l’endothélium et de la eNOS, est augmentée en condition pulsée à une force de cisaillement de 20 dyn/cm2. En présence de PEG-catalase, la dilatation induite par le flux est diminuée en pression statique mais pas en pression pulsée, suggérant que la pression statique, mais pas la pression pulsée, favorise la production de O2 -/H2O2. En effet, la dilatation induite par le flux est associée à une production de O2 -/H2O2 par la eNOS, mesurable en pression statique, alors que la dilatation induite par le flux en pression pulsée est associée à la production de NO. Les différences de sensibilité à la dilatation induite par le flux ont été abolies après inhibition de Nox2, en condition statique ou pulsée. La pression pulsée physiologique régule donc l’activité de la eNOS cérébrale, en augmentant le tonus myogénique et, en présence de flux, permet la relâche de NO via la eNOS. / While in vivo arterial blood pressure in cerebral arteries is pulsatile, in vitro cerebral arterial function is generally assessed under a static pressure. Thus, whether pulse pressure regulates cerebral endothelial shear stress sensitivity and myogenic tone is unknown. We hypothesized that a physiological pulse pressure induces a better flow-mediated dilation and optimized myogenic tone. The aim of this study was to test in vitro the impact of pulse pressure on myogenic tone and eNOS-dependent flow-mediated dilation in mouse cerebral arteries. Using a custom computer-controlled pneumatic system generating a pulse pressure (used at 30 mm Hg, rate of 550 bpm) coupled to an arteriograph, isolated posterior cerebral arteries from 3-month old C57Bl/6J mice were pressurized at 60 mm Hg, either in static or pulse pressure conditions. Shear stress from 2 to 20 dyn/cm2 was applied and flow-mediated dilation measured. Without pulse pressure, myogenic tone was low but potentiated by both L-NNA (eNOS inhibitor) and PEG-catalase (catalyses H2O2), suggesting an influence of eNOS-derived dilator products on myogenic tone. Pulse pressure significantly increased myogenic tone, independently of L-NNA and PEG-catalase, suggesting that pulse pressure prevents the impact of eNOS. In both static and pulse pressure conditions, cerebral arteries did not dilate to shear stress in the presence of L-NNA or after endothelial denudation, confirming the endothelial origin of the dilatory response. Up to 15 dyn/cm2, shear stress elicited similar flow-mediated dilation in static and pulse pressure conditions; at 20 dyn/cm2, however, flow-mediated dilation were higher in the presence of pulse pressure. PEG-catalase reduced flow-mediated dilation in static but not in pulse pressure, suggesting that in static conditions eNOS is responsible for O2 -/H2O2 production. Indeed, eNOS-derived O2 -/H2O2 production was measured during flow-mediated dilation in static pressure, while pulse pressure promoted eNOS-derived NO production. Differences in flow-mediated dilation between static and pulse pressure conditions were abolished after Nox2 inhibition. In conclusion, pulse pressure modulates cerebrovascular eNOS activity: at rest, pulse pressure inhibits eNOS, increasing myogenic tone. In the presence of flow, pulse pressure permits a shear stress-dependent eNOS-derived NO release, leading to higher flow-mediated dilation.

Le comportement à long terme des excavations souterraines est un enjeu social et économique majeur, en particulier dans le contexte du stockage en formation géologique profonde de déchets nucléaires à Haute Activité et Vie Longue (HAVL). Plusieurs galeries expérimentales ont été creusées dans le laboratoire de recherche souterrain de Meuse/Haute-Marne situé près de Bure en France, où des études sont menées pour comprendre le comportement global de la roche constitutive : l’argilite du Callovo-Oxfordien (COx).L’objectif de cette thèse est d’effectuer une modélisation avec Code_Aster d’ouvrages souterrains, et en particulier d’une des galeries du laboratoire de Meuse/Haute-Marne, en prenant en compte une approche non locale, l’effet du fluage et le couplage hydromécanique dans le cadre de la mécanique des milieux poreux, et de comparer les résultats numériques avec les données expérimentales disponibles.Le modèle élastoviscoplastique spécifiquement utilisé pour cette étude est le modèle L&K : il offre d’une part un couplage entre le comportement instantané et différé, et prend en compte d’autre part la dilatance, paramètre qui gouverne les déformations volumiques du matériau lors d’une sollicitation, et ses fortes variations, caractéristique essentielle des géomatériaux et en particulier du COx. La présence d’un fluide s’écoulant à travers le matériau va ajouter une composante hydraulique à la modélisation, dont le couplage avec la mécanique est assuré par les équations de Biot. Une autre nouveauté de ce travail concerne le couplage entre ce comportement rhéologique complexe et une approche non locale dans un cadre industriel. Parmi les méthodes de régularisation disponibles dans Code_Aster, la méthode second gradient de dilatation a été choisie parce que bien adaptée aux géomatériaux. Son but est de corriger la dépendance au maillage et les solutions numériques localisées.Une fois les outils numériques opérationnels et les paramètres du modèle L&K calés sur des essais effectués en laboratoire sur des échantillons, un bon accord général a été trouvé entre les résultats numériques et les mesures in situ, sans aucun recalage des paramètres. Les effets du temps observés expérimentalement sur l’évolution des déplacements et des pressions d’eau sont retrouvés au sein d’une même modélisation, validant ainsi la démarche prédictive suivie / The long term behaviour of underground excavations is a social and economic stake, in particular in the context of storage in deep geological formation of high activity and long life nuclear waste. Several experimental galleries have been dug in the underground research laboratory (URL) of Meuse/Haute-Marne located close to Bure in France, where studies are leaded in order to understand the global behaviour of the constitutive rock which is the Callovo-Oxfordian (COx) argillite.The purpose of this PhD Thesis is to establish a modelling with Code_Aster of underground excavations, and especially of a Meuse/Haute-Marne laboratory gallery, taking into account non local approach, creep effect and hydromechanical coupling in the framework of the mechanics of porous media, and then to compare numerical results with available experimental data.The specific elastoviscoplastic model used in this study is the L&K model: it offers a coupling between instantaneous and delayed behaviour, and it takes into account the dilation, parameter which governs the volume strains of the material during a solicitation, and its strong variation, a specificity of geomaterials and so of COx argillite. The fluid flowing through the material adds a hydraulic component to the modelling, which is coupled to mechanic component thanks to Biot’s equations.Another novelty of this work concerns the coupling between such complex rheological behaviour and a non local approach in an industrial way. Among methods of regularization available in Code_Aster, the second gradient of dilation is well fitted to geomaterials. Its aim is to correct mesh dependency and numerical localized solutions.After describing numeric tools and setting parameters of the L&K model on laboratory tests, a good general agreement was found between numeric results and in situ measures, without resetting parameters. Time effects experimentally measured on displacement and pore pressure evolution are observed in the same modelling, validating the followed predictive approach

As hard rock mining progresses into higher stress mining conditions through either late stage extraction or mining at depth, the rock mass is driven not just to the peak strength, but often well into the post-peak until complete ‘failure’ occurs and easier mining conditions become evident. Limited research has been accomplished in identifying the transition of the rock mass and its behaviour into the post-peak and this research investigates this behaviour in detail. As the rock mass progressively fails, fractures are initiated through intact rock and extension and shear failure of these and pre-existing features occurs. Associated with this failure are microseismic events, which can be used to give an indication of the strength state of the rock mass. Based on an analogy to laboratory testing of intact rock and measurement of acoustic emissions, the microseismicity can be used to identify, fracture initiation, coalescence of fractures (yield), localization (peak-strength), accumulation of damage (post-peak) and ultimate failure (residual strength) leading to aseismic behaviour. The case studies presented in this thesis provide an opportunity to examine and analyse rock mass failure into the post-peak, through the regional and confined failures at the Williams and the Golden Giant mines, both in the Hemlo camp in Northern Ontario, Canada. At the Williams mine, the progressive failure of a sill pillar region into the post-peak was analysed; relating the seismic event density, combined with numerical modelling and a spatial and temporal examination of the principal components analysis (PCA), to characterize the extent, trend and state of the yielding zone, which formed a macrofracture shear structure. Observations of conventional displacement instrumentation, indicates regional dilation or shear of the rock mass occurs at or prior to the point of ‘disassociation’ (breakdown of stable PCA trends) when approaching the residual strength. At the Golden Giant mine, the complete process from initiation to aseismic behaviour is monitored in a highly stressed and confined pendent pillar. The PCA technique, numerical modelling and focal mechanism studies are used to define significant stages of the failure process, in which a similar macrofracture structure was formed. Temporal observations of key source parameters show significant changes prior to and at the point of coalescence and localization.

Ce travail de thèse est consacré à l'étude des renforts textiles techniques 2D à l'échelle mésoscopique. La méthode des éléments finis est utilisée pour résoudre un problème aux limites, fortement non linéaire, dans le domaine du renfort fibreux. Deux nouveaux modes de déformations pour le comportement des mèches de renforts ont été développés et caractérisés. Le premier mode est la compression longitudinale, qui permet de traduire la faible rigidité des mèches lorsqu'elles subissent une dilatation négative dans le sens des fibres. La relation conflictuelle sur le plan numérique entre la rigidité en tension, très forte, et la rigidité en compression longitudinale, très faible, peut être résolue via trois méthodes : réduction du pas de temps critique, addition de la contribution en tension ou avec une nouvelle stratégie pour l'actualisation du champ de contrainte. Le second mode de déformation est la dilatation transversale des mèches considérée comme conséquence directe de la compression longitudinale. Ce phénomène d'expansion de matière dans les directions transverses peut être observé avec un essai de compression longitudinale in-situ sous tomographie X et est communément ignorer. Un protocole expérimental a été mise en place pour mesurer cette dilatation transversale des mèches et un coefficient de Poisson a pu être caractérisé par identification inverse. Une campagne expérimentale a permis d'identifier les paramètres matériau du modèle mésoscopique et les résultats de simulations sont comparés aux images issues d'essai mécanique in situ sous tomographe. / This thesis is devoted to the mesoscopic study on the performance of textile reinforcements. F.E. simulation is carried out on a mesoscale model for the fibrous material, based on which two kinds of new deformation modes are developed. The first one is a longitudinal compression mode, which is used to reflect the small stiffness when the yarn is compressed longitudinally. The incompatibility problem between the small longitudinal compression stiffness and the large tension stiffness are solved by three different strategies: constraining the critical step time, adding the nonlinear tension part, or using a new strategy to update the stress. The second one is transverse expansion mode that could reflect the influence from longitudinal deformation to transverse deformation. This deformation could be found in tomography view but was ignored by the former researches. An experiment is designed to measure the expansion magnitude, and the geometrical inverse fitting process is applied to measure the value of the longitudinal-transverse Poisson ratio. The parameters of the mesoscale model are measured by a series of mechanical experiments and the simulation results are verified by the tomography methodology.

A disfunção erétil (DE) tem alta prevalência entre hipertensos e tem sido considerada marcador precoce de risco cardiovascular. A presença e gravidade da DE bem como a resposta clínica aos inibidores da fosfodiesterase tipo 5 (PDE5) parecem depender da biodisponibilidade do óxido nítrico (NO) endotelial e da extensão da doença aterosclerótica. O objetivo deste estudo foi avaliar a resposta clínica da vardenafila usada em dois regimes terapêuticos em hipertensos com DE vasculogênica e sem doença cardiovascular maior, correlacionando a gravidade da DE e a eficácia da vardenafila com dados antropométricos, laboratoriais, escore de risco cardiovascular e parâmetros vasculares funcionais e estruturais. A resposta clínica à vardenafila nos dois regimes foi avaliada conforme o percentual de respostas positivas à questão 3 do Perfil do Encontro Sexual (PES3). Os parâmetros vasculares considerados foram a espessura médio-intimal (EMI) da carótida comum, a dilatação mediada pelo fluxo (DMF) da artéria braquial e a dilatação nitrato-mediada (DNM). Foram incluídos 100 homens hipertensos com idade entre 50 e 70 anos, sendo 74 portadores de DE vasculogênica e 26 com função erétil normal que serviram de grupo controle. Nos pacientes com DE, o índice de massa corporal, relação cintura-quadril, EMI da carótida, níveis séricos de triglicerídeos, colesterol total e LDL foram significativamente maiores que no grupo controle. Após o uso de vardenafila on demand (fase 1), os pacientes com mais de 50% de respostas positivas ao PES3 ou 50% de respostas afirmativas e um incremento de 6 pontos ou mais em relação ao Índice Internacional de Função Erétil (IIEF-FE) basal e/ou resposta positiva a Questão de Avaliação Global (QAG), foram considerados respondedores. O escore do IIEF-FE basal se correlacionou negativamente com a EMI da carótida (r=-0,48, P<0,001) e com o escore de Framingham (r= -0,41, P<0,001) no grupo com DE. Houve forte correlação positiva entre a resposta clínica à vardenafila com a DMF (r= 0,70, P<0,001), que não se observou entre o sub-grupo de diabéticos. Os 35 pacientes considerados não-respondedores na fase 1 foram randomizados e, em desenho duplo-cego, receberam vardenafila ou placebo diariamente durante cinco semanas, podendo usar 10 mg de vardenafila uma hora antes da atividade sexual (fase2). Houve resposta clínica positiva em 38,8% dos que receberam a vardenafila na fase 2 e esta resposta se correlacionou com a frequência sexual (r= 0,68, P<0,01) e com o escore de Framingham (r= -0,65, P<0,01), com a EMI da carótida (r= -0,61, P=0,01) e com o LDL-colesterol (r= -0,64, P<0,01). A vardenafila foi bem tolerada em ambos os regimes terapêuticos. Concluímos que nessa amostra de hipertensos, a gravidade da DE foi relacionada a parâmetros vasculares estruturais (EMI), enquanto a resposta clínica à vardenafila on demand foi mais diretamente dependente da função vascular momentânea (DMF). Houve benefício na utilização de vardenafila diariamente com o objetivo de resgatar a eficácia do inibidor quanto à melhora do desempenho sexual. A falta de eficácia clínica ao inibidor da PDE5 em ambos os regimes terapêuticos pode servir como marcador clínico que identifica homens hipertensos com um risco cardiovascular aumentado. / Erectile dysfunction (ED) is a high prevalent disease in hypertensive subjects and has been considered an early cardiovascular risk marker. EDs presence and severity, as well as clinical response to phosfodiesterase type 5 (PDE5) inhibitors, vary according to nitric oxide (NO) availability and atherosclerosis extension. We investigated whether vasculogenic ED severity and clinical response to vardenafil used on demand or continuously were associated with structural and functional vascular changes in patients with uncomplicated hypertension. Our main efficacy criterion was per patient percentage of positive answers on Sexual Encounter Profile question 3(SEP3). Vascular parameters considered were intima-media thickness (IMT), flow-mediated dilation (FMD) on brachial artery and nitrate-mediated dilation. A total of 100 hypertensive men aging between 50 and 70 years were included. Among these patients, 74 had vasculogenic ED and 26 presented normal erectile function according to erectile domain of International Index of Erectile Function (IIEF-EF). Among those with ED, body mass index, waist-rip ratio, carotid IMT, triglycerides, total cholesterol and LDL-cholesterol were significantly higher than controls. After vardenafil on demand usage during phase 1, patients with more than 50% of positive answers on SEP3 or 50% and more than 6 points on IIEF basal score or positive answer to global evaliation question were considered responders. IIEF basal score correlated inversely with carotid IMT (r=-0.48, P<0.001) and with Framingham risk score (r= -0.41, P<0.001) in ED group. Clinical response to vardenafil strongly correlated with FMD (r= 0.70, P<0.001), except among diabetics. Non responders (n=35) on phase 1 were included on phase 2 when, after randomization, they received vardenafil 10 mg nightly or placebo during five weeks. Open vardenafil on demand were allowed one hour before sexual intercourse, and 38.8% of active group improved and became responders to vardenafil. Clinical response on phase 2 correlated with sexual frequency (r= 0.68, P<0.01), Framingham score (r= -0.65, P<0.01), carotid IMT (r= -0.61, P=0.01) and LDL-cholesterol (r= -0.64, P<0.01). We concluded that in hypertensive males with vasculogenic ED and no other clinical evidence of atherosclerosis, ED severity correlated with structural parameters (carotid IMT), while phosphodiesterase-5 effectiveness correlated with functional vascular aspects (brachial FMD). There were positive impact with continuous vardenafil on non responders to on demand regime and that could be an option to salvage strategy. Lack of PDE5 inhibitor efficacy in both therapeutic strategies could point out to higher cardiovascular risk and could be considered a useful clinical marker.

A disfunção erétil (DE) tem alta prevalência entre hipertensos e tem sido considerada marcador precoce de risco cardiovascular. A presença e gravidade da DE bem como a resposta clínica aos inibidores da fosfodiesterase tipo 5 (PDE5) parecem depender da biodisponibilidade do óxido nítrico (NO) endotelial e da extensão da doença aterosclerótica. O objetivo deste estudo foi avaliar a resposta clínica da vardenafila usada em dois regimes terapêuticos em hipertensos com DE vasculogênica e sem doença cardiovascular maior, correlacionando a gravidade da DE e a eficácia da vardenafila com dados antropométricos, laboratoriais, escore de risco cardiovascular e parâmetros vasculares funcionais e estruturais. A resposta clínica à vardenafila nos dois regimes foi avaliada conforme o percentual de respostas positivas à questão 3 do Perfil do Encontro Sexual (PES3). Os parâmetros vasculares considerados foram a espessura médio-intimal (EMI) da carótida comum, a dilatação mediada pelo fluxo (DMF) da artéria braquial e a dilatação nitrato-mediada (DNM). Foram incluídos 100 homens hipertensos com idade entre 50 e 70 anos, sendo 74 portadores de DE vasculogênica e 26 com função erétil normal que serviram de grupo controle. Nos pacientes com DE, o índice de massa corporal, relação cintura-quadril, EMI da carótida, níveis séricos de triglicerídeos, colesterol total e LDL foram significativamente maiores que no grupo controle. Após o uso de vardenafila on demand (fase 1), os pacientes com mais de 50% de respostas positivas ao PES3 ou 50% de respostas afirmativas e um incremento de 6 pontos ou mais em relação ao Índice Internacional de Função Erétil (IIEF-FE) basal e/ou resposta positiva a Questão de Avaliação Global (QAG), foram considerados respondedores. O escore do IIEF-FE basal se correlacionou negativamente com a EMI da carótida (r=-0,48, P<0,001) e com o escore de Framingham (r= -0,41, P<0,001) no grupo com DE. Houve forte correlação positiva entre a resposta clínica à vardenafila com a DMF (r= 0,70, P<0,001), que não se observou entre o sub-grupo de diabéticos. Os 35 pacientes considerados não-respondedores na fase 1 foram randomizados e, em desenho duplo-cego, receberam vardenafila ou placebo diariamente durante cinco semanas, podendo usar 10 mg de vardenafila uma hora antes da atividade sexual (fase2). Houve resposta clínica positiva em 38,8% dos que receberam a vardenafila na fase 2 e esta resposta se correlacionou com a frequência sexual (r= 0,68, P<0,01) e com o escore de Framingham (r= -0,65, P<0,01), com a EMI da carótida (r= -0,61, P=0,01) e com o LDL-colesterol (r= -0,64, P<0,01). A vardenafila foi bem tolerada em ambos os regimes terapêuticos. Concluímos que nessa amostra de hipertensos, a gravidade da DE foi relacionada a parâmetros vasculares estruturais (EMI), enquanto a resposta clínica à vardenafila on demand foi mais diretamente dependente da função vascular momentânea (DMF). Houve benefício na utilização de vardenafila diariamente com o objetivo de resgatar a eficácia do inibidor quanto à melhora do desempenho sexual. A falta de eficácia clínica ao inibidor da PDE5 em ambos os regimes terapêuticos pode servir como marcador clínico que identifica homens hipertensos com um risco cardiovascular aumentado. / Erectile dysfunction (ED) is a high prevalent disease in hypertensive subjects and has been considered an early cardiovascular risk marker. EDs presence and severity, as well as clinical response to phosfodiesterase type 5 (PDE5) inhibitors, vary according to nitric oxide (NO) availability and atherosclerosis extension. We investigated whether vasculogenic ED severity and clinical response to vardenafil used on demand or continuously were associated with structural and functional vascular changes in patients with uncomplicated hypertension. Our main efficacy criterion was per patient percentage of positive answers on Sexual Encounter Profile question 3(SEP3). Vascular parameters considered were intima-media thickness (IMT), flow-mediated dilation (FMD) on brachial artery and nitrate-mediated dilation. A total of 100 hypertensive men aging between 50 and 70 years were included. Among these patients, 74 had vasculogenic ED and 26 presented normal erectile function according to erectile domain of International Index of Erectile Function (IIEF-EF). Among those with ED, body mass index, waist-rip ratio, carotid IMT, triglycerides, total cholesterol and LDL-cholesterol were significantly higher than controls. After vardenafil on demand usage during phase 1, patients with more than 50% of positive answers on SEP3 or 50% and more than 6 points on IIEF basal score or positive answer to global evaliation question were considered responders. IIEF basal score correlated inversely with carotid IMT (r=-0.48, P<0.001) and with Framingham risk score (r= -0.41, P<0.001) in ED group. Clinical response to vardenafil strongly correlated with FMD (r= 0.70, P<0.001), except among diabetics. Non responders (n=35) on phase 1 were included on phase 2 when, after randomization, they received vardenafil 10 mg nightly or placebo during five weeks. Open vardenafil on demand were allowed one hour before sexual intercourse, and 38.8% of active group improved and became responders to vardenafil. Clinical response on phase 2 correlated with sexual frequency (r= 0.68, P<0.01), Framingham score (r= -0.65, P<0.01), carotid IMT (r= -0.61, P=0.01) and LDL-cholesterol (r= -0.64, P<0.01). We concluded that in hypertensive males with vasculogenic ED and no other clinical evidence of atherosclerosis, ED severity correlated with structural parameters (carotid IMT), while phosphodiesterase-5 effectiveness correlated with functional vascular aspects (brachial FMD). There were positive impact with continuous vardenafil on non responders to on demand regime and that could be an option to salvage strategy. Lack of PDE5 inhibitor efficacy in both therapeutic strategies could point out to higher cardiovascular risk and could be considered a useful clinical marker.